Agreed there are other factors, but if Vince is going to make generalizations about high versus low SHBG then we have to agree to fix the other variables, unless you can demonstrate they are linked to SHBG. My statement is meant to apply when metabolic clearances are the same except for the influence of differing levels of free testosterone, which are caused by differing levels of SHBG.
Ok, here's the first claim: two guys chosen at random on TRT with the same doses: Relative SHBG levels between the guys will not be predictive of relative free testosterone. The relevant variables are independent of SHBG. These variables are the rate of absorption of the testosterone ester from the injected depots and the components of the metabolic clearance rate that are independent of free testosterone.
I'm still waiting for the first substantive argument from you on this subject. Useful peer review requires more than a knee-jerk negative reaction.
I am pretty sure that the interaction between testosterone and aromatase occurs only when the testosterone is free. But don't think of SHBG as a permanent jail. It's a reservoir that releases testosterone when free levels drop.
It's plausible that there would be focal high-T spots at the injection sites. But in general the cleaving of testosterone from the ester occurs in the bloodstream. It's a slow and steady process, unless you happened to do an IV injection. Otherwise the absorption rate from the injected depots is driving everything (free T, etc.), and this is much slower than other processes.
As long as it's accurate, free T is more important than total. For those whose SHBG doesn't change much then total can have similar utility. Getting accurate free T is a matter of either paying for an equilibrium dialysis test or using the Tru-T calculator to get a good estimate from total T and SHBG.
Wait what? This is new to me. From what I always understood, a higher SHBG results in lower free T, because higher SHBG binds up more of the T, so you get lower free T. Conversely, lower SHBG will bind up less of the T, leaving the patient with higher free T. And you are saying that this is not true?
This is true. It applies when you are considering a fixed total serum testosterone; free testosterone has an inverse relationship with SHBG.
Gotcha. But isn't what you said earlier saying something different? "" Ok, here's the first claim: two guys chosen at random on TRT with the same doses: Relative SHBG levels between the guys will not be predictive of relative free testosterone. ""
The statements are consistent. If you choose guys who have the same total testosterone then SHBG does predict free testosterone. But that is quite different from choosing guys at random. Mathematically, SHBG and free T are the independent random variables, while total T is dependent. We're used to thinking of total testosterone as the driver, but my argument is that it's more appropriate to say that free testosterone is in control. In TRT our injections set free T. And in a normal HPTA, regulation is based on free T, not total T.
I'm following you now. Thanks for elaborating for me.
